Analysis of paracetamol tablets using a calibration curve

Tablets

Tablets contain paracetamol 500 mg, phenylpropanolamine 5 mg.

Explanation of the assay

Even without chromatographic resolution the small amount of phenylpropanolamine present in

the formulation could be disregarded since its A(1%, 1 cm) value at the wavelength 243 nm used
for monitoring paracetamol is ca 4 compared to an A(1%, 1 cm) of 668 for paracetamol. An
ODS column retains paracetamol adequately if the amount of water in the mobile phase is high.
Thus the mobile phase used is 0.05 M acetic acid/acetonitrile (90:15); the weakly acidic mobile
phase ensures there is no tendency for the phenol group in paracetamol (pKa 9.5) to ionise. The
tablet extract has to be diluted sufficiently to bring it within the range of the UV detector.

Fig. 12.22
(A) Extract from paracetamol
tablets in comparison with (B)
paracetamol standard at about the
same concentration. Column:
octadecylsilyl (ODS) 4.6
mm×150 mm, mobile phase
acetonitrile: 0.05 M acetic acid
(85:15) flow rate 1 ml/min.
(SF¼solvent front).

12.22 shows the chromatographic traces obtained for an extract from paracetamol tablets and a
paracetamol standard (1.25 mg/100 ml) run using the system described above.

Assay

(i) Weigh out 12510 mg of the paracetamol standard and transfer it to a 250 ml
volumetric flask made up to volume with acetic acid (0.05 M) and shake well (stock
solution).
(ii) Prepare a series of solutions containing 0.5, 1.0, 1.5, 2.0 and 2.5 mg/100 ml of
paracetamol from the stock solution.
(iii) Weigh and powder 20 tablets.
(iv) Weigh out tablet powder containing 125 mg10 mg of paracetamol.
(v) Shake the tablet powder sample with ca 150 ml of acetic acid (0.05 M) for 5 min in a
250 ml volumetric flask and then adjust the volume to 250 ml with more acetic acid
(0.05 M).
(vi) Filter ca 50 ml of the solution into a conical flask and then transfer a 25 ml aliquot of
the filtrate to 100 ml volumetric flasks and adjust the volume to 100 ml with acetic
acid (0.05 M).
(vii) Take 10 ml of the diluted extract and transfer to a further 100 ml volumetric flask and
make up to volume with 0.05 M acetic acid.
(viii) Analyse the standards and the extract using the chromatographic conditions specified
earlier.

Data obtained
• Weight of 20 tablets¼12.1891 g
• Weight of tablet powder taken¼150.5 mg
• Weight of paracetamol calibration standard¼126.1 mg
• Area of paracetamol peak extracted from tablets¼45 205.
Calculate the percentage of the stated content of paracetamol in the tablet powder
analysed.
The graph shown in Figure 12.23 is obtained from the data given in Table 12.6; it
is linear with r¼1.000.
The equation of the line can be used to calculate the amount of paracetamol in the
diluted extract of the tablet powder.

Fig. 12.23
Calibration curve
for the
determination of
paracetamol in
tablets obtained
from high-
performance liquid
chromatography
(HPLC) analysis of
calibration
standards
 Table 12.6 Data obtained from the analysis of paracetamol standard solutions
by high-performance liquid chromatography (HPLC)
Concentration of paracetamol Area of chromatographic peak
standard solution mg/100 ml
0.5044 17 994
1.009 36 109
1.513 54 121
2.018 71 988
2.522 89 984

Calculation example 12.4

Substituting the area obtained for the paracetamol peak obtained from the analysis of the
tablet powder extract into the equation for the line:

45 205 = 35 656x + 80

Solving for x gives the concentration of the extract in mg/100 ml.

1 45205−80
Concentration of paracetamol in diluted tablet extract ¿ =1.266mg/100ml.
35656 2

Dilution steps

The dilution steps used were:

• 25 ml into 100 ml (× 4)
• 10 ml into 100 ml (× 10)
• Total = × 40.

Calculation example 12.4 (Continued)

Concentration of paracetamol in undiluted tablet extract

1.266mg/100ml = 40 = 50.64mg/100ml

Amount of paracetamol in undiluted tablet extract

• The volume of the undiluted tablet extract=250 ml

• Amount of paracetamol in 100 ml of the extract=50.64 mg

• Amount of paracetamol in 250 ml of extract=250/100×50.64 mg=126.6 mg

• Amount of paracetamol found in the tablet powder assayed=126.6 mg.

Amount of paracetamol expected in the tablet powder taken for assay

• Weight of 20 tablets=12.1891 g

• Weight of one tablet=12.1891/20=0.6094 g =609.5 mg

• Stated content per tablet=500 mg

• Amount of paracetamol expected in the weight of tablet powder taken for

assay=150.5/609.5×500 mg=123.5 mg.

Percentage of stated content

• Percentage of stated content=126.6/123.5×100=102.5%.